What is the next step in managing a patient with polycythemia?

Elevated Hemoglobin/Hematocrit in a 62-Year-Old Female: Next Steps

The next step is to measure serum erythropoietin (EPO) level, as this patient's hemoglobin of 16.7 g/dL and hematocrit of 50.6% exceed diagnostic thresholds for polycythemia vera (PV), which requires evaluation starting with EPO measurement followed by bone marrow examination if indicated. 1, 2

Why This Patient Requires Evaluation

• Hemoglobin >16.0 g/dL in women meets diagnostic criteria for erythrocytosis and warrants investigation for PV 3
• The hematocrit of 50.6% is significantly above the 95th percentile of normal distribution for females, triggering the need for diagnostic workup 1, 2
• At age 62, this patient falls into a higher-risk category if PV is confirmed, as age >60 years is a major risk factor for thrombotic complications 3, 4

Diagnostic Algorithm

Step 1: Serum Erythropoietin Level

• Low EPO (specificity >90%): Highly suggestive of PV and warrants proceeding to bone marrow examination 1, 2
• Normal EPO: Does not rule out PV (sensitivity of low EPO for PV is <70%), still proceed to bone marrow examination 5, 1
• High EPO: Indicates need to evaluate for secondary polycythemia causes 1, 2

Step 2: Assess for PV-Related Features

Before proceeding with invasive testing, evaluate for:

• Thrombocytosis or leukocytosis (present in 53% and 49% of PV patients respectively) 3
• Microcytosis suggesting iron deficiency, which can mask the true degree of erythrocytosis 1, 2
• Splenomegaly (present in 36% of PV patients) 3
• Symptoms: aquagenic pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%) 3
• History of unusual thrombosis including Budd-Chiari syndrome 1, 2

Step 3: Bone Marrow Examination (if EPO low or normal)

• Bone marrow histology should assess for: hypercellularity, increased megakaryocytes with cluster formation, giant megakaryocytes with pleomorphic morphology, and decreased iron stores 1, 2
• Cytogenetic studies have limited diagnostic value (abnormalities in only 13-18% at diagnosis) 5, 1

Step 4: JAK2 Mutation Testing

• More than 95% of PV patients have a JAK2 mutation (JAK2V617F or exon 12 mutations), which helps distinguish PV from secondary causes 3, 6
• This test is highly valuable for confirming the diagnosis 6

If Secondary Polycythemia is Suspected (High EPO)

Evaluate for:

• Hypoxia-driven causes: chronic lung disease, sleep apnea, smoking (carbon monoxide exposure), high altitude 5, 2
• Pathologic EPO production: renal cell cancer, hepatocellular carcinoma, uterine leiomyoma, pheochromocytoma 5, 2
• Congenital causes: high oxygen-affinity hemoglobinopathy 5, 2
• Drug-associated: EPO doping, androgen preparations 5, 2

Measure arterial hemoglobin-oxygen saturation and carboxyhemoglobin level, and consider imaging of kidneys, liver, and CNS to rule out EPO-producing tumors 2

Critical Pitfalls to Avoid

• Do not rely on red cell mass (RCM) measurement: It is costly, redundant when hematocrit >60%, and a normal RCM does not rule out PV 5, 1, 2
• Do not use traditional markers alone: Splenomegaly, leukocytosis, thrombocytosis, elevated leukocyte alkaline phosphatase, and increased vitamin B12 levels lack sensitivity and specificity 5, 1
• Do not miss iron deficiency: Low MCHC may indicate iron deficiency that is masking the true degree of erythrocytosis 1
• Do not delay evaluation: 16% of PV patients have arterial thrombosis and 7% have venous thrombosis at or before diagnosis, including unusual sites like splanchnic veins 3

Urgency of Evaluation

This patient requires prompt evaluation because:

• Median survival from diagnosis is 14-27 years, but untreated patients may survive only 6-18 months 3, 7
• Thrombosis risk is immediate: The hyperviscosity from elevated hematocrit predisposes to thrombotic events 7
• Age >60 years places her in the high-risk category for thrombotic complications if PV is confirmed 3, 4